During the past few years there has been an alarming increase in adolescent and teen-age ethanol (ETOH) abuse and a growing concern for its possible medical consequences. One of the most fascinating aspects of endocrinology occurs during this period of time and that is the complex series of events that lead to reproductive maturity. The overall goal of the proposed studies is to obtain information which will allow us to better understand the detrimental effects and mechanism(s) of action of ETOH on the pubertal process. Both in vivo and in vitro techniques will be used following chronic or acute ETOH exposure to answer the following specific aims or questions: a) what effect does ETOH have on specific neuropeptides and neuromodulators known to affect GH and LH release via hypothalamic actions and how does each correlate with pubertal onset, b) what are the effects of specific growth factors at the time of puberty and what effect does ET0H have on them, c) what effect will ET0H have on the pubertal process and hormonal substances involved following longer exposure and what is the prognosis of recovery or reversibility following removal of the drug from the diet, d) can specific exogenously administered neuropeptides or other neuromodulators, or growth factors override the detrimental effects of ETOH on puberty, e) what effect does ETOH have on the content of specific ovarian peptides necessary for ovarian maturity and what effect does ETOH have on ovarian responsiveness to specific peptides and gonadotropins and f) development of a cell culture system for growing specialized populations of hypothalamic neurons for studying the neurotoxic effects of ETOH on specific neuropeptide secreting cells of which their function is necessary for the timely onset of puberty and sexual development. These experiments should allow us to make much progress in understanding mechanisms involved with ETOH's detrimental effect on the onset of puberty.